2-201138287-T-C

Variant names:

• chr2-201138287-T-C
• rs7560613
• ENST00000395148.6:c.*1860T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000309955.8(CFLAR):​c.524-2070T>C variant causes a intron change. The variant allele was found at a frequency of 0.19 in 787,886 control chromosomes in the GnomAD database, including 16,941 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (5170 hom., cov: 32)
  • Exomes 𝑓: 0.18 (11771 hom.)
• Consequence: CFLAR ENST00000309955.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.80
• Publications: 7 publications found

Genes affected

CFLAR (HGNC:1876): (CASP8 and FADD like apoptosis regulator) The protein encoded by this gene is a regulator of apoptosis and is structurally similar to caspase-8. However, the encoded protein lacks caspase activity and appears to be itself cleaved into two peptides by caspase-8. Several transcript variants encoding different isoforms have been found for this gene, and partial evidence for several more variants exists. [provided by RefSeq, Feb 2011]

IMPDH1P10 (HGNC:33965): (inosine monophosphate dehydrogenase 1 pseudogene 10)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000309955.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	NM_003879.7	MANE Select	c.524-2070T>C		intron	N/A	NP_003870.4
	CFLAR	NM_001308043.2		c.*1860T>C		3_prime_UTR	Exon 5 of 5	NP_001294972.1
	CFLAR	NM_001127183.4		c.524-2070T>C		intron	N/A	NP_001120655.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	ENST00000395148.6	TSL:1	c.*1860T>C		3_prime_UTR	Exon 5 of 5	ENSP00000378580.2
	CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.524-2070T>C		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.524-2070T>C		intron	N/A	ENSP00000399420.2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36260 AN: 151816 Hom.: 5151 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.179 AC: 113693 AN: 635952 Hom.: 11771 Cov.: 7 AF XY: 0.178 AC XY: 61481 AN XY: 345344

African (AFR) AF: 0.393 AC: 6982 AN: 17752

American (AMR) AF: 0.124 AC: 5370 AN: 43250

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 5284 AN: 20438

East Asian (EAS) AF: 0.00391 AC: 140 AN: 35836

South Asian (SAS) AF: 0.129 AC: 9032 AN: 69802

European-Finnish (FIN) AF: 0.140 AC: 6993 AN: 49946

Middle Eastern (MID) AF: 0.189 AC: 507 AN: 2682

European-Non Finnish (NFE) AF: 0.201 AC: 72959 AN: 363538

Other (OTH) AF: 0.196 AC: 6426 AN: 32708

GnomAD4 genome AF: 0.239 AC: 36329 AN: 151934 Hom.: 5170 Cov.: 32 AF XY: 0.233 AC XY: 17339 AN XY: 74286

African (AFR) AF: 0.392 AC: 16246 AN: 41400

American (AMR) AF: 0.173 AC: 2649 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 959 AN: 3466

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5174

South Asian (SAS) AF: 0.116 AC: 558 AN: 4806

European-Finnish (FIN) AF: 0.132 AC: 1398 AN: 10570

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13759 AN: 67932

Other (OTH) AF: 0.228 AC: 481 AN: 2108

Alfa AF: 0.128 Hom.: 225

Bravo AF: 0.247

Asia WGS AF: 0.109 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.56
PhyloP100		3.8
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7560613; hg19: chr2-202003010;